Method and compositions for solubilizing non-polar constituents

ABSTRACT

A method for solubilizing non-polar target compounds into a carrier liquid is described. A carrier oil, such as a MCT, or a mixture of MCTs, may be used to solubilize non-polar target compounds. The carrier oil may also include one or more buffers for stability of the target compounds within the carrier oil.

BACKGROUND OF THE INVENTION State of the Art

The present disclosure relates to a method which may be used tosolubilize non-polar constituents. The disclosure also relates to thesolutions/compositions formulated via the subject solubilizationprocess, to the method for preparing same, to the resulting compositionscontaining the non-polar constituents thus solubilized, and to theadministration thereof.

Electronic nicotine delivery systems (ENDS) have grown in popularity inrecent years. In 2014, ENDS usage surpassed traditional cigarette usagein young people in the United States. Hildick-Smith, Gordon J.; Pesko,Michael F.; Shearer, Lee; Hughes, Jenna M.; Chang, Jane; Loughlin,Gerald M.; Ipp, Lisa S. (2015). “A Practitioner's Guide to ElectronicCigarettes in the Adolescent Population.” Journal of Adolescent Health,57: 574-9. Most commonly, ENDS work by heating a liquid to its boilingpoint, vaporizing the liquid for the user to inhale.

Typically, the carrier liquid used in ENDS consists of a combination ofvegetable glycerin and propylene glycol, along with a “flavor,” and/ornicotine. Flavors or additives known in the art are limited to thosewhich may be solubilized in vegetable glycerin or a combination ofvegetable glycerin and propylene glycol. Additives may also be limitedby their boiling point, as a compound with a high boiling point cancreate an uncomfortable hot vaping experience in order to vaporize thecompound.

While it may be desirable to have additives that are non-polar orstrongly non-polar, there are currently no known methods in the art forsolubilizing such compounds within the known carrier liquid, asvegetable glycerin and propylene glycol are both polar compounds.Additionally, although propylene glycol may have emulsifying qualities,its hydrophilic-lipophilic balance may be insufficient to stabilize manynon-polar compounds.

SUMMARY OF THE INVENTION

The present disclosure may provide a method to solubilize targetcompounds, such as non-polar compounds, in a carrier liquid for use inENDS.

The present disclosure includes multiple different methods, systems, andapplications which can be used to solubilize non-polar target compoundsand are thus applications of a common inventive concept. It should beappreciated that various devices, systems, methods and applications willhave some benefits and may lack other benefits which are present indifferent devices, systems, methods and applications. Therefore, theteachings of the present disclosure and any actual or intended benefitof any embodiments should not be read into the claims unless expresslystated therein.

According to one aspect of the present disclosure, the carrier liquid tobe used to solubilize the target compound may comprise a mixture ofdifferent types of medium chain triglycerides (MCT), in the range ofC6-C12. The target compound may be any suitable non-polar compound andin some aspects, the non-polar compound is one of riboflavin,sulbutiamine, and cannabidiol.

According to one aspect, a method is described to solubilize non-polartarget compounds, the method comprising admixing a medium chaintriglyceride carrier liquid and a non-polar target compound. Mixing themedium chain triglyceride carrier liquid and the non-polar targetcompound may form an azeotropic mixture, which may allow a lower, morepleasant temperature of vaporization, and may allow a cleanervaporization for improving the useful life of the device.

According to another aspect, the carrier liquid and the non-polar targetcompound may be mixed in several different ratios, depending on thetarget compound. For example, the carrier liquid and the non-polartarget compound may be mixed in a ratio of about 0.01:99.99. Or thecarrier liquid and the non-polar target compound may be mixed in a ratioof about 95:5. or mixed in a ratio of about 50:50.

In some configurations, the medium chain triglyceride carrier liquid maycomprise a mixture of C6-C12 medium chain triglycerides. For example,the medium chain triglyceride carrier liquid may be comprised of atleast one of approximately 0-6.0% hexanoic acid, 6.0-60% octanic acid,and 6.0-60% decanoic acid, where the medium length fatty acids may beincorporated into the glycerol backbone of the triglyceride.

According to another aspect, the method may further comprise adding anamount of buffer to the carrier liquid. Similarly, the method maycomprise adding an amount of acid to the carrier liquid, or adding anamount of two or more buffers to the carrier liquid. The buffer may havea molar concentration of around 0.01-10 mM in the carrier liquid.

Also disclosed herein is a composition for use in an electronic nicotinedelivery system, the composition comprising a non-polar target compoundand a carrier liquid comprised of one or more medium chaintriglycerides. The composition may comprise approximately 0.01 to 70percent non-polar target compound and 30 to 99.99 percent carrierliquid. Other percentages are possible as well. For example, 30 to 70percent non-polar target compound may be use with 70 to 30 percentcarrier liquid.

The non-polar target compound of the composition may comprise essentialoils, for example, monoterpenes, triterpenes, sesquiterpenes, and/orditerpenes. According to another configuration, the non-polar targetcompound may comprise at least one of riboflavin, sulbutiamine, andcannabidiol.

According to another aspect of the disclosure, the carrier liquid of thecomposition may comprise a mixture of at least one or more oftriglycerides composed of one or more of the following fatty acids (on aglycerol backbone to form the triglyceride): hexanoic acid, octanicacid, decanoic acid, and dodecanoic acid. In some compositions, thecarrier liquid may comprise about 0-6 percent triglycerides composed ofhexanoic acid, 6-60 percent triglycerides composed of octanic acid, and6-60 percent triglycerides composed of decanoic acid.

Small amounts, such as 0.00% to 30% of branched-chain fatty acids, suchas lanolin. may be added in order to increase viscosity. Lanolincontains a high proportion of iso and ante/so fatty acids from C₁₀ toC₃₄ in chain length including an ante/so-branched fatty acid,18-methyl-eicosanoic acid, which constitutes up to 60% of the totalfatty acids.

According to yet another aspect, a vapor cartridge is disclosedcontaining a composition comprising a non-polar target compound and acarrier liquid comprised of one or more medium chain triglycerides. Thecartridge may further comprise a wick, such as a cotton wick or othertype of wick, or non-wick vaporization system.

These and other aspects of the present invention are realized in amethod for solubilizing non-polar constituents as shown and described inthe following figures and related description.

DETAILED DESCRIPTION

The skilled artisan will understand that the methods described below canbe practiced without employing these specific details, or that they canbe used for purposes other than those described herein. Indeed, they canbe modified and can be used in conjunction with products and techniquesknown to those of skill in the art in light of the present disclosure.

Reference in the specification to “one configuration,” “one embodiment”“one aspect” or “a configuration,” “an embodiment” or “an aspect” meansthat a particular feature, structure, or characteristic described inconnection with the configuration may be included in at least oneconfiguration and not that any particular configuration is required tohave a particular feature, structure or characteristic described hereinunless set forth in the claim. The appearances of the phrase “in oneconfiguration” or similar phrases in various places in the specificationare not necessarily all referring to the same configuration, and may notnecessarily limit the inclusion of a particular element of the inventionto a single configuration, rather the element may be included in otheror all configurations discussed herein. Thus it will be appreciated thatthe claims are not intended to be limited by the representativeconfigurations shown herein. Rather, the various representativeconfigurations are simply provided to help one of ordinary skill in theart to practice the inventive concepts claimed herein.

Furthermore, the described features, structures, or characteristics ofembodiments of the present disclosure may be combined in any suitablemanner in one or more embodiments. In the following description,numerous specific details may be provided, such as examples of productsor manufacturing techniques that may be used, to provide a thoroughunderstanding of embodiments of the invention. One skilled in therelevant art will recognize, however, that embodiments discussed in thedisclosure may be practiced without one or more of the specific details,or with other methods, compounds, materials, and so forth. In otherinstances, well-known structures, materials, or operations may not beshown or described in detail to avoid obscuring aspects of theinvention.

Before the present invention is disclosed and described in detail, itshould be understood that the present invention is not limited to anyparticular structures, process steps, or materials discussed ordisclosed herein. More specifically, the invention is defined by theterms set forth in the claims. It should also be understood thatterminology contained herein is used for the purpose of describingparticular aspects of the invention only and is not intended to limitthe invention to the aspects or embodiments shown unless expresslyindicated as such. Likewise, the discussion of any particular aspect ofthe invention is not to be understood as a requirement that such aspectis required to be present apart from an express inclusion of that aspectin the claims.

It should also be noted that, as used in this specification and theappended claims, singular forms such as “a,” “an,” and “the” may includethe plural unless the context clearly dictates otherwise. Thus, forexample, reference to “a bracket” may include an embodiment having oneor more of such brackets, and reference to “the target plate” mayinclude reference to one or more of such target plates.

As used herein, the term “substantially” refers to the complete ornearly complete extent or degree of an action, characteristic, property,state, structure, item, or result to function as indicated. For example,an object that is “substantially” enclosed would mean that the object iseither completely enclosed or nearly completely enclosed. The exactallowable degree of deviation from absolute completeness may in somecases depend on the specific context, such that enclosing the nearly allof the length of a lumen would be substantially enclosed, even if thedistal end of the structure enclosing the lumen had a slit or channelformed along a portion thereof. The use of “substantially” is equallyapplicable when used in a negative connotation to refer to the completeor near complete lack of an action, characteristic, property, state,structure, item, or result. For example, structure which is“substantially free of” a bottom would either completely lack a bottomor so nearly completely lack a bottom that the effect would beeffectively the same as if it completely lacked a bottom.

As used herein, the term “about” is used to provide flexibility to anumerical range endpoint by providing that a given value may be “alittle above” or “a little below” the endpoint while still accomplishingthe function associated with the range.

As used herein, a plurality of items, structural elements, compositionalelements, and/or materials may be presented in a common list forconvenience. However, these lists should be construed as though eachmember of the list is individually identified as a separate and uniquemember.

Concentrations, amounts, proportions and other numerical data may beexpressed or presented herein in a range format. It is to be understoodthat such a range format is used merely for convenience and brevity andthus should be interpreted flexibly to include not only the numericalvalues explicitly recited as the limits of the range, but also toinclude all the individual numerical values or sub-ranges encompassedwithin that range as if each numerical value and sub-range is explicitlyrecited. As an illustration, a numerical range of “about 1 to about 5”should be interpreted to include not only the explicitly recited valuesof about 1 to about 5, but also include individual values and sub-rangeswithin the indicated range. Thus, included in this numerical range areindividual values such as 2, 3, and 4 and sub-ranges such as from 1-3,from 2-4, and from 3-5, etc., as well as 1, 2, 3, 4, and 5,individually. This same principle applies to ranges reciting only onenumerical value as a minimum or a maximum. Furthermore, such aninterpretation should apply regardless of the breadth of the range orthe characteristics being described.

The invention and will now be so as to enable one skilled in the art topractice the present invention. The descriptions are intended to beexemplary of various aspects of the invention and are not intended tonarrow the scope of the appended claims.

As used herein, “electronic nicotine delivery system” or “ENDS” meansany type of device that may be used to vaporize a solution forinhalation of the vapors, whether or not the solution contains nicotine.Such systems include, for example, electronic cigarettes, vapingdevices, advanced personal vaporizers, etc.

As used herein, “MCT” or “MCTs” means medium-chain triglycerides. It mayrefer to one type of medium-chain triglyceride, or it may refer to amixture of different types of medium-chain triglycerides. For example,it may refer to a solution of a single type of medium-chain triglycerideof a particular length, or it may refer to a mixture of medium-chaintriglycerides with different compositions and/or lengths.

As used herein, the term “target compound” means a compound to be addedto a carrier liquid or carrier oil to be used in an ENDS. The targetcompound may be a non-polar compound. For example, target compounds maycomprise non-polar essential oils, non-polar compounds that exist assolids at room temperature, compounds that are insoluble in vegetableglycerin and propylene glycol, compounds that vaporize at a highertemperature than vegetable glycerin and propylene glycol, and compoundsthat form an azeotrope with medium-chain triglycerides. Essential oiltarget compounds may include monoterpenes, diterpenes, andsesquiterpenes.

As used herein, “carrier oil” or “carrier liquid” refers to the liquidused to solubilize the target compound. Carrier oil and carrier liquidare used interchangeably herein. The carrier oil may comprise a mixtureof different MCTs, such as a mix of C6-C12 MCTs, or it may comprise asingle type of medium-chain triglyceride. The carrier liquid may haveother additives, such as additives that increase the stability of thecarrier liquid. A variety of MCTs may be used, such as MCT formed from 2or 3 of the fatty acid chains attached to glycerol which are of mediumlength. Both branched and unbranched fatty acids may be used, as well assaturated and unsaturated. Typically, 2 to 3 chains of the medium chaintrygylceride may be hexanoic acid, octanoic acid, decanoic acid, and/ordodecanoic acid.

As used herein, “solubilization of a target compound” means a dispersionin the molecular state in a carrier liquid.

Solubilization of target compounds may be achieved by the use of acarrier liquid that is azeotropic with the target compounds. Standardazeotropes have a boiling point either higher or lower than any of itsindividual components. Most commonly for the present disclosure, theazeotropes have a lower boiling point than their components.Additionally, an azeotrope retains the same composition in the vaporstate as in the liquid state. By using an azeotrope, the temperature atwhich the target compound may be vaporized is lowered. This may allowtarget compounds to be used in ENDS which would otherwise vaporize at atemperature that was too high. Additionally, the azeotrope is suitablefor use in an ENDS because the proportions of the constituents of thecomposition of the liquid state and the vapor state are the same.

In order to form an azeotrope with the target compounds, different typesof carrier liquids may be used. For example, blends of medium-chaintriglycerides, formed of medium-chain fatty acids with aliphatic tailsof 6-12 carbons, were found to be azeotropic with many target compounds.Depending on the desired results, different blends of the medium-chaintriglycerides may be used. For example, triglycerides formed ofmedium-chain fatty acids with aliphatic tails of 6 carbons (C6triglycerides) may be desirable as a low molecular weight oil that maydecrease the viscosity and modify the flow rate through the wick of theENDS, improve the stability of dissolved target compounds againsttemperature changes, and/or improve the solubility of target compounds.Thus, a blend that includes some C6 triglycerides, between 0.01% and30%, along with other MCTs, may be beneficial, compared to usingentirely C6 triglycerides.

Varying the proportion of chain-length of the triglyceride varies theviscosity of the carrier oil. An oil that lacks proper viscosity mayleak from the ENDS. and one that is too viscous may cause wickstarvation. Varying the concentrations or proportions of differentchain-lengths of triglycerides may allow for tailoring of a carrier oilthat has a good flow rate that minimizes prevents wick starvation andleakage from the ENDS.

The amount of target compound and the amount of carrier fluid may alsobe varied. For example, a mixture of approximately 50/50 targetcompound/carrier fluid has been found to be azeotropic with a lowerboiling point. Other concentrations may also be used. For example, amixture of 5/95 target compound/carrier fluid may be azeotropic, as wellas a mixture of 60/40 target compound/carrier fluid. According toanother aspect of the present disclosure, a component may be added tothe carrier liquid/target compound mixture in order to providestability. This may be necessary, for example, when using targetcompounds that contain carboxylic functional groups. Carboxylic acidshave labile hydrogen atoms which can dissociate and leave the moleculein a more polar ionized state. These ionized or “activated” carboxylicacids can be retained on certain types of wicks, including cotton orsynthetic wicks, which are common in the vape market. This can inhibitthe flow of the molecules containing a carboxylic acid into the heatingchamber, and can also lead to the accumulation of the molecules on thewick, which inhibits flow. By adding a stabilizing compound, the labilehydrogen atoms may be more stabilized, preventing ionized carboxylicacids that may be retained on wicks.

It is well known that when organic acids are in an environment that ismore than 2 points of pH above their pK_(a) they will be greater than99% ionized and therefore, more polar and more likely to be retained ona polar substrate, such as a cotton wick. The present disclosurecontemplates buffering the carrier oil with a small amount of astabilizing buffer formula—usually less than 0.1% v/v or w/w. The bufferformula may vary with the pK_(a) of the solubilized organic acid.Additionally, one or more buffers may be used. For example, two buffersmay be employed to create a basin of stability around the solubilizedtarget compound. This is important in the event of contamination, forexample, when MCT oil is added to the cartridge of an ENDS or when thereservoir of the ENDS contains a residual volume of a previous vapingliquid.

In addition to buffers, other stabilizing compounds may be added to thecarrier oil depending on the target compound. For example, organicbases, organic acids, buffers, etc. may be used. In the case of a targetcompound that is an organic acid, it may be desirable to add astabilizer, such as a buffer, to fix the pH of the solution at or aroundat least 1 pH point below the pK_(a) of the target compounds in order toensure that no acidic target compounds are ionized. Alternatively,stabilization may be acidification, without the use of a buffer. Forexample, an organic acid may be used in very small amounts (typical lessthan 0.1% w/w). In the case of a target compound that is an organicbase, it may be desirable to add a stabilizer, such as a buffer, to fixthe pH of the solution, to minimize interaction with certain wickmaterials.

The solubility of buffers and organic acids in the carrier oil isanother consideration. Most organic acids are not miscible intriglyceride oils, but there is be some degree of solubility for organicacids such as formic and acetic acids. Propionic, butyric and valericacids possess strong goaty aromas and may be objectionable to consumers.It has been discovered that at least a small amount of buffer, organicacid, and/or organic base may be dissolved in a carrier oil/targetcompound mix, and that even a small amount of buffer may advantageouslyprovide stability to the target compounds to minimize unwanted depositson the wick. 0.01-10 mM is usually sufficient for the purposes ofstabilizing the target compound in the carrier oil.

Organic acids possessing some solubility in triglyceride oils include:valeric acid, caproic acid, caprylic acid, capric acid, benzoic acid,lauric acid, Myristic acid, palmitic acid and stearic acid.

An aspect of the invention may include buffers with some solubility inthe carrier oil. Benzoic acid may be useful for stabilizing targetcompounds in the present disclosure. The pKa of Benzoic acid is about4.2 with solubility in the carrier oil of approximately 4 gm/100 g andlog P (partition co-efficient) of about 1.9. It is typically employed ata level of 0.01 to 0.1% by weight. In use, the raw carrier oil is heatedto 85-100 degrees Celsius for 10 minutes. The benzoic acid is then addedwith stirring and the heat is maintained for about 5 minutes. This maybe a typical first step in the preparation of the targetcompound-carrier oil co plexation. This pre-heating of the carrier oilallows any residual moisture to be driven off before the addition ofbenzoic acid. In some cases of use, the flavor of benzoic acid iscloying. In those cases, phenylacetic acid may be used which possesses ahoney-like aroma. It has a pKa and log P comparable to benzoic acid andcan be complexed in a similar manner.

Benzyl alcohol may be added to the carrier oil in small amounts (forexample, 0.01% to 5%) to improve the clarity and solubility of manytarget compounds. In addition this method can improve the solubility andclarity of room-temperature solid organic acids such as lauric, myristicand palmitic acids, buffers listed above and room-temperature solidterpenes such as certain diterpenes, sesquiterpenes and triterpenes aswell as the terpenoids. In fact, small amounts of benzyl alcohol canimprove buffer solubility of weakly acidic buffers in the carrier oilwith good stability (low tendency to form esters) so long as noinorganic acids are present.

According to another aspect, compounds may be added to further stabilizethe carrier oil. For example, free radical processes can degradetriglycerides. This can cause changes in the stability of the vape oil.In some cases, such as where solubilized compounds bring labile hydroxylgroups and moisture in contact with MCTs, saponification can occur.According to one aspect, drying of a carrier and/or components andchoice of compounds can limit the occurrence of moisture. The avoidanceof hygroscopic compounds and compounds that form moisture when theybreak down, and/or the inclusion of compounds that absorb moisture orinterfere with hydrolysis make increase stability. In general thestabilization of pH to ensure non-ionized triglycerides helps to controlrancidification and saponification, but some target components mayrequire the addition of certain reducing compounds. Filtering oil duringblending of components, such as through a small amount of borax orsodium borohydride may improve stability. The inclusion of oil miscibleanti-oxidants, such as lutein, lycopene and ascorbyl palmitate, mayfurther improve stability.

Exposure to sunlight or UV light may also cause breakdown. Thus, smallamounts of USP singlet-quenching compounds, such as lycopene (moreeffective for excited singlet suppression than vitamin-E), may be usedto reduce the formation of free radicals. Reducing the life of excitedsinglet-states can reduce the formation of long-lived triplet radicalsby reducing intersystem-crossing.

The process for solubilizing target compounds according to thedisclosure comprises, in particular, the following steps: (a)preparation of a carrier liquid solution comprising a mixture ofmedium-chain triglycerides, an amount of this carrier liquid solution isused, the amount depending on the amount of target compound to besolubilized; (b) admixing the carrier liquid solution with the targetcompound; (c) and, optionally, admixing a stabilizing compound to thecarrier liquid/target compound. In some cases, depending on the compoundto be solubilzed, solvents that dissolve both polar and non-polarcompounds such as ethanol, methanol, acetonitrile, 1-butanol orisopropyl alcohol, may be added to encourage solubilization, and thenremoved by vacuum evaporation. As another aspect, during compounding,dry inert gas may be filtered through the mixture to remove moisture.

Examples

The present disclosure contemplates many types of carrier oils andnon-polar target compounds. The range of compounds that may beeffectively used in ENDS is vastly expanded as a result of using thenon-polar carrier oil described herein. The following specific examplesare given for illustration, and do not limit the scope of the claims.

Riboflavin is known to have poor solubility in aqueous solutions andorganic solvents. In vegetable glycerin, propylene glycol and water, thesolubility of riboflavin is less than 0.2 mg/ml. It may be desirable tosolubilize a higher concentration of riboflavin in an ENDS. Solubilityof riboflavin may be improved slightly by alkaline buffering, howeverthis dramatically reduces the stability of riboflavin to time,temperature, and UV light. However, greater solubility may be achievedby heating a mixture of methanol and riboflavin to 55-60 degreesCelsius. This mixture may then be added to MCTs (for example 0.0-6.0%C6, 6.0-60% C8, and/or 6.0-60% C10), homogenized for 5 minutes andsubsequently heated to approximately 85 degrees Celsius at 250 mb (or250 hPa) pressure in a rotary evaporator to drive off the methanol. Thismay achieve an order of magnitude greater solubility for riboflavin inMCTs versus aqueous solutions.

Another example may be sulbutiamine. Sulbutiamine is a disulfide dimerof thiamine. It is insoluble in aqueous solutions but highly soluble infats. It may be desirable to provide sulbutiamine in an ENDS. Forexample, a stable solution of 200 mg/mL sulbutiamine in MCTs (forexample, 0.0-6.0% C6, 6.0-60% C8, and/or 6.0-60% C10) may be created bysimple stirring the solution at 85 degrees Celsius for 5 minutes.Solutions of higher concentration may be possible, for example, by usingthe method described above (using one or more solvents that dissolveboth polar and non-polar compounds such as ethanol, methanol,acetonitrile, 1-butanol or isopropyl alcohol, may be added to encouragesolubilization, and then removing the solvent(s) by vacuum evaporation).

Another example may be cannabidiol, which is currently being researchedas an investigative new drug by GW Pharmaceuticals, for use in seizureconditions and other diseases. Should GW Pharmaceutical be grantedfurther approval for cannabidiol, or should cannabidiol receives widerapproval status, it may be medically desirable for certain patients toreceive cannabidiol from an ENDS in vapor form, since this providesarguably the fastest non-invasive route of delivery. Cannabidiol may besolubilized up to about 80 percent v/v in MOTs (for example 0.0-6.0% C6,6.0-60% C8, and/or 6.0-60% C10) by simply stirring at 45 to 65 degreesCelsius for 5 minutes.

Another example may be diinolylmethane (DIM). DIM is a naturallyoccurring non-polar compound in cruciferous brassica vegetables. DIMcurrently has interesting investigative properties in such areas ascancer, infectious diseases, and immune deficiency conditions. Inparticular, DIM has been investigated for its value in recurrentrespiratory pappillomatosis, a condition caused by the human papillomavirus. DIM's delivery and bioavailability is limited by its non-polarnature. DIM may be solubilized by admixing 0.01 to 15% with MCT at 65degrees centigrade. Higher percentages of DIM may be dissolved DIM maybe combined with the isoflavone Genistein and prepared in the samemanner. The two compounds, taken together, have enhanced value in theinhibition of tumor growth.

Another example may be vitamin-D3, which can simply be admixed in anyproportion with the stabilized, viscosity adjusted carrier oil.

Another example may be a combination of oil soluble antioxidants such aslycopene, lutein and ascorbyl palmitate. For example, a stable solutionof 200 mg/mL lycopene, lutein, and/or ascorbyl palmitate in MCTs (forexample, 0.0-6.0% C6, 6.0-60% C8, and/or 6.0-60% C10) may be created bysimple stirring the solution at 85 degrees Celsius for 5 minutes.Solutions of higher concentration may be possible, for example, by usingthe method described above (using one or more solvents that dissolveboth polar and non-polar compounds such as ethanol, methanol,acetonitrile, 1-butanol or isopropyl alcohol, may be added to encouragesolubilization, and then removing the solvent(s) by vacuum evaporation).

Another example may be a combination of tocotrienol, alpha-carotene andxanthins, such as Zeaxanthin, Astaxanthin, Crytoxanthin andCanthaxanthin. These are powerful antioxidants that provide benefits invarious tissues of the human body. They may be incorporated into thecarrier oil by admixing in small quantities (<2 mg/ml) (or in largerquantities using the method described above using one or more solventsthat dissolve both polar and non-polar compounds such as ethanol,methanol, acetonitrile, 1-butanol or isopropyl alcohol, may be added toencourage solubilization, and then removing the solvent(s) by vacuumevaporation similar to section 0044, where the solvent to be evaporatedmay be among those listed or may include among others, ethyl-acetate,dimethyllformamide, dichloroethane and trichloroethane).

Another example may be a combination of mono-terpenes, mono-terpenoids,di-terpenes, di-terpenoids and sesquiterpenes. Mono-terpenes are readilysoluble in the carrier oil and may simply be admixed in any ratio attemperatures from 10-65 degrees Celsius, depending on the species.Monoterpenoids, diterpenes, diterpenoids and sesquiterpenes may requirehomogenization, solvent addition and evaporation (using one or moresolvents that dissolve both polar and non-polar compounds such asethanol, methanol, acetonitrile, 1-butanol or isopropyl alcohol, may beadded to encourage solubilization, and then removing the solvent(s) byvacuum evaporation).

Terpenes have many desirable effects in human physiology. Linaloolimproves muscle relaxation. Beta-Caryophyllene reduces pain.Beta-Myrcene can improve the transport of many compounds across theblood-brain barrier. The diterpenoid retinal has benefits as an animalform of vitamin-A.

Monoterpenes, including acyclic monoterpenes, monocyclic monoterpense,and bicyclic monoterpenes may be solubilized according to the methoddescribed herein. For example, a list of exemplary monoterpenes that maybe included by admixing at 10-65 degrees Celsius in proportions of0.0001% to 60% monoterpene in 99.9999% to 40% MCTs includes: Ascaridole;Bornane; Borneol; Camphene; Camphor; Carene; Carvacrol; Carveol;Carvone; Carvonic acid; Chrysanthemic acid; Chrysanthenone; Citral;Citronellal; Citronellol; Cuminaldehyde; P-Cymene; Cymenes; Epomediol;Eucalyptol Fenchol; Fenchone; Geranic acid; Geraniol; Geranyl acetate;Geranyl pyrophosphate; Grapefruit mercaptan; Halomon; Hinokitiol;8-Hydroxygeraniol; Incarvillateine; (S)-Ipsdienol; Jasmolone;Lavandulol; Lavandulyl acetate; Levoverbenone; Limonene; Linalool;Linalyl acetate; Lineatin; P-Menthane-3,8-diol; Menthofuran; Menthol;Menthone; Menthoxypropanediol; Menthyl acetate; 2-Methylisoborneol;Myrcene; Myrcenol; Nerol; Nerolic acid; Ocimene; 8-Oxogeranial;Paramenthane hydroperoxide; Perilla ketone; Perillaldehyde;Perillartine; Perillene; Phellandrene; Picrocrocin; Pinene;Alpha-Pinene; Beta-Pinene; Piperitone; Pulegone; Rhodinol; Rose oxide;Sabinene; Safranal; Sobrerol; Terpinen-4-ol; Terpinene; Terpineol;Thujaplicin; Thujene; Thujone; Thymol; Thymoquinone; Umbellulone;Verbenone; and Wine lactone.

A list of exemplary diterpenes that may be solubilized at temperaturesfrom 15-85 degrees Celsius, as in section 0044, in proportions from0.0001% to 60% includes: Abietane; Abietic acid; Agelasimine; Agelasine;Andrographolide; Aphidicolin; Beta-Araneosene; Bipinnatin J; Cafestol;Carnosic acid; Carnosol; Cembrene A; Clerodane diterpene;10-Deacetylbaccatin; EBC-46; Erinacine; Ferruginol; Fichtelite;Forskolin; Galanolactone; Geranylgeraniol; Geranylgeranyl pyrophosphate;Gibberellin; Ginkgolide; Grayanotoxin; Guanacastepene A; Ingenolmebutate; Isocupressic acid; Isopimaric acid; Isotuberculosinol;Kahweol; KM-233; Labdane; Lagochilin; Laurenene; Leelamine; Levopimaricacid; Menatetrenone; Momilactone B; Neotipterifordin; 18-Norabietane;Panicudine; Phorbol; Phorbol 12,13-dibutyrate; Phyllocladane; Phytane;Phytanic acid; Phytol; Pimaric acid; Pristane; Pristanic acid;Prostratin; Pseudopterosin A; Retinol; Ryanodine; Salvinorin; Sclarene;Sclareol; Shortolide A; Simonellite; Stemarene; Stemodene; Steviol;Taxadiene; Taxamairin A; Taxodone; Tenuifolin;12-O-Tetradecanoylphorbol-13-acetate; Tetrahydrocannabinol-C4;Tetrahydrocannabinolic acid; Totarol; Tricholomalide; Tripchlorolide;Tripdiolide; Triptolide; and Triptolidenol.

The list of exemplary diterpenoids that may be solubilized attemperatures from 15-85 degrees Celsius, by admixing (or using one ormore solvents that dissolve both polar and non-polar compounds such asethanol, methanol, acetonitrile, 1-butanol or isopropyl alcohol, toencourage solubilization, and then removing the solvent(s) by vacuumevaporation), in proportions from 0.0001% to 60%, is large with hundredsof skeletons and thousands of species (such as retinol, phytol).

A list of exemplary sesquiterpenes that may be solubilized attemperatures from 15-85 degrees Celsius, as in section 0044, inproportions from 0.0001% to 60% includes: Abscisic acid;Amorpha-4,11-diene; Aristolochene; Artemether; Artemotil; Artesunate;Bisabolene; Bisabolol; Botrydial; Cadalene; Cadinene; Alpha-Cadinol;Delta-Cadinol; Capnellene; Capsidiol; Carotol; Caryophyllene; Cedrene;Cedrol; Copaene; Cubebol; Curdione; Curzerene; Curzerenone;Dictyophorine; Drimane; Elemene; Farnesene; Farnesol; Farnesylpyrophosphate; Germacrene; Germacrone; Guaiazulene; Guaiene; Guaiol;Gyrinal; Hernandulcin; Humulene; Indometacin farnesil; Ionone;Isocomene; Juvabione; Ledol; Longifolene; Mutisianthol; Nardosinone;Nerolidol; Nootkatone; Norpatchoulenol; Onchidal; Patchoulol;Periplanone B; Petasin; Phaseic acid; Polygodial; A-Santalol;B-Santalol; Santonic acid; Selinene; Spathulenol; Thujopsene;Tripfordine; Triptofordin C-2; Valencene; Velleral; Verrucarin A;Vetivazulene; A-Vetivone; and Zingiberene.

Another example may be the addition of Omega-3 fatty acids by admixing,at temperatures between 15-65 degrees Celsius, to the carrier oil.Specific examples include Eicospentaenoic acid, Docosahexaenoic acid, inproportions from 0.01% to 70%.

Another example may be the addition of fatty acids, such as linoleic andlinolenic acid, by admixing at temperatures between 15-65 degreescentigrade, to the carrier oil. Fatty acids are easily rancidified butcan be stabilized with methods, such as singlet quenchers andantioxidants described herein.

Another example may be the addition of cannabinoids other thancannabidiol, the diterpene Tetrahydracanabinol and its acid to thecarrier oil. Over 100 cannabinoids have been discovered. These can beadmixed to the carrier oil at 45 to 65 degrees Celsius for 5 minutes toachieve complete dissolution.

There is thus disclosed a method for solubilizing non-polar targetcompounds in a carrier liquid suitable for use in an ENDS. It will beappreciated that numerous modifications may be made without departingfrom the scope and spirit of this disclosure. The appended claims areintended to cover such modifications.

What is claimed is:
 1. A method for solubilizing a diterpene, the method comprising: admixing the diterpene and a medium chain triglyceride carrier liquid comprised of at least one of 0-6.0% of the triglyceride form of hexanoic acid, 6.0-60% of the triglyceride form of octanic acid, and 6.0-60% of the triglyceride form of decanoic acid to form an azeotropic solution; adding an amount of buffer to the carrier liquid; and heating the azeotropic solution in a heated vaporization delivery system to vaporize the azeotropic solution.
 2. The method of claim 1, wherein the carrier liquid and the diterpene are mixed in a ratio of about 50:50 v/v.
 3. The method of claim 1, wherein the method further comprises adding an amount of acid to the carrier liquid.
 4. The method of claim 1, wherein the method further comprises adding an amount of two or more buffers to the carrier liquid.
 5. The method of claim 1, wherein the buffer has a molar concentration of around 0.01-10 mM in the carrier liquid.
 6. The method of claim 1, wherein the carrier liquid and the diterpene are mixed in a ratio of about 0.01:99.99 v/v.
 7. The method of claim 1, wherein the carrier liquid and the diterpene are mixed in a ratio of about 95:5 v/v.
 8. The method of claim 1, wherein admixing the medium chain triglyceride carrier liquid and the diterpene forms an azeotropic mixture, wherein the carrier liquid and the diterpene are mixed in a ratio of about 50:50 v/v, and wherein the method further comprises adding at least one buffer to the carrier liquid, wherein the at least one buffer a molar concentration of around 0.01-10 mM in the carrier liquid.
 9. The method of claim 8, further comprising the step of adding an oil miscible anti-oxidant to the carrier liquid.
 10. The method of claim 1, wherein the diterpene comprises tetrahydracanabinol.
 11. A composition for use in an electronic nicotine delivery system, the composition comprising: a non-polar target compound, the non-polar target compound comprising a diterpene; a carrier liquid comprised of one or more medium chain triglycerides comprised of at least one of about 0-6.0% of the triglyceride form of hexanoic acid, about 6.0-60% of the triglyceride form of octanic acid, and about 6.0-60% of the triglyceride form of decanoic acid; and at least one buffer having a molar concentration of around 0.01-10 mM in the carrier liquid.
 12. The composition of claim 11, wherein the diterpene comprises tetrahydracanabinol.
 13. The composition of claim 11, wherein the composition comprises approximately 40 to 60 percent non-polar target compound and 40 to 60 percent carrier liquid.
 14. The composition of claim 11, wherein the carrier liquid comprises a mixture of at least two or more of the triglyceride forms of: hexanoic acid, octanic acid, decanoic acid, and dodecanoic acid.
 15. The composition of claim 11, wherein the composition comprises an azeotropic mixture having an azeotropic temperature of vaporization, and wherein the azeotropic temperature of vaporization is lower than a temperature of vaporization of the non-polar target compound and lower than a temperature of vaporization of carrier liquid.
 16. The composition of claim 15, wherein the composition comprises approximately 40 to 60 percent diterpene and 40 to 60 percent carrier liquid, and wherein the carrier liquid comprises an azeotropic mixture of the medium chain triglyceride carrier liquid.
 17. The composition of claim 11, further comprising an oil miscible anti-oxidant.
 18. A vapor cartridge for use in a heated vaporization system, the vapor cartridge containing a composition comprising; a non-polar target compound, the non-polar target compound comprising a diterpene; at least one buffer; and a carrier liquid comprised of one or more medium chain triglycerides comprised of at least one of the triglyceride forms of 0-6.0% hexanoic acid, 6.0-60% octanic acid, and 6.0-60% decanoic acid.
 19. The vapor cartridge of claim 18, further comprising an oil miscible anti-oxidant.
 20. The vapor cartridge of claim 18, wherein the diterpene comprises tetrahydracanabinol. 